Recurrent metastatic patterns and prognosis after radical surgery in patients with alpha-fetoprotein-producing gastric cancer: a retrospective cohort study.

Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the recurrent metastatic patterns and prognostic factors in AFPGC patients undergoing radical surgical resection. Data from 241 AFPGC patients diagnosed between January 2017 and January 2020 who underwent surgical resection were analyzed across multiple centers. Recurrence patterns, metastatic sites, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify risk factors for recurrent metastasis, overall survival (OS), and disease-free survival (DFS). There is an annual increase in the proportion of AFPGC cases, rising from 3.45% in 2017 to 7.88% in 2023. Higher serum AFP level was associated with increased likelihood of lymph node metastasis (P=0.006), deeper invasion depth (P=0.000) and greater tumor diameter (P=0.036). Independent predictors of recurrent metastasis included T4 infiltration, lymph node metastasis, tumor diameter >5 cm, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP levels. The 5-year OS and DFS rates were 36.5% and 34.2%, respectively, with poorer survival linked to higher preoperative AFP levels and postoperative increasing trend in AFP level. Independent risk factors for poor OS and DFS included T4 infiltration, lymph node metastasis, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP. Serum AFP level can serve as a potential predictive and prognostic biomarker. Identifying independent risk factors informs risk stratification and personalized treatment for AFPGC patients.

Experience of psychosocial rehabilitation; perspectives of depressed adolescents.

Given the multifaceted character of depression and its related symptoms, an adolescent living with it is at increased risk for a wide range of adverse events. This research aimed to understand and characterize the psychosocial rehabilitation experiences of depressed teenage participants in the Greater Accra Region of Ghana. A cross-sectional semi-structured interview design influenced by an interpretive phenomenological analysis (IPA) technique was adopted. We employed a nonprobability, purposeful sampling approach to recruit twenty-one adolescents (6 males, 15 females) diagnosed with depression from the community after one month of discharge from admission and undergoing psychosocial rehabilitation. Using separate interviews, we gathered and analyzed data using interpretive phenomenological analysis to produce themes and sub-themes. These were presented with the participants' direct quotations. We discovered that the perspectives of adolescents' psychosocial rehabilitation experience include hopelessness and suicide ideation, coping difficulties, undesirable attitudes from support networks, challenges related to school, and isolation. Participants suggested appropriate therapeutic environments, encouraging support systems, and the media's role in preventing and treating depression among young people as rehabilitation approaches that could assist adolescents to remain lucid for longer intervals. These results shed light on the tragic realities faced by depressed adolescents. There is an urgent need to put well-defined structures in place to aid their rehabilitation and develop coping strategies for a better life.

Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial.

OBJECTIVE: To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy. DESIGN: Randomised, double blind, placebo controlled, phase 3 study. SETTING: 146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023. PARTICIPANTS: 1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease. INTERVENTIONS: Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator's choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator's choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity. MAIN OUTCOME MEASURES: The primary endpoint was overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment. RESULTS: Of 1657 patients screened between 13 December 2018 and 9 February 2021, 660 were ineligible due to not meeting the eligibility criteria, withdrawal of consent, adverse events, or other reasons. Overall, 997 were randomly assigned to receive tislelizumab plus chemotherapy (n=501) or placebo plus chemotherapy (n=496). Tislelizumab plus chemotherapy showed statistically significant improvements in overall survival versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5% (median 17.2 months v 12.6 months; hazard ratio 0.74 (95% confidence interval 0.59 to 0.94); P=0.006 (interim analysis)) and in all randomised patients (median 15.0 months v 12.9 months; hazard ratio 0.80 (0.70 to 0.92); P=0.001 (final analysis)). Grade 3 or worse treatment related adverse events were observed in 54% (268/498) of patients in the tislelizumab plus chemotherapy arm versus 50% (246/494) in the placebo plus chemotherapy arm. CONCLUSIONS: Tislelizumab added to chemotherapy as primary treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5%, and in all randomised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03777657.

The RNA-Binding Protein BoRHON1 Positively Regulates the Accumulation of Aliphatic Glucosinolates in Cabbage.

Aliphatic glucosinolates are an abundant group of plant secondary metabolites in Brassica vegetables, with some of their degradation products demonstrating significant anti-cancer effects. The transcription factors MYB28 and MYB29 play key roles in the transcriptional regulation of aliphatic glucosinolates biosynthesis, but little is known about whether BoMYB28 and BoMYB29 are also modulated by upstream regulators or how, nor their gene regulatory networks. In this study, we first explored the hierarchical transcriptional regulatory networks of MYB28 and MYB29 in a model plant, then systemically screened the regulators of the three BoMYB28 homologs in cabbage using a yeast one-hybrid. Furthermore, we selected a novel RNA binding protein, BoRHON1, to functionally validate its roles in modulating aliphatic glucosinolates biosynthesis. Importantly, BoRHON1 induced the accumulation of all detectable aliphatic and indolic glucosinolates, and the net photosynthetic rates of BoRHON1 overexpression lines were significantly increased. Interestingly, the growth and biomass of these overexpression lines of BoRHON1 remained the same as those of the control plants. BoRHON1 was shown to be a novel, potent, positive regulator of glucosinolates biosynthesis, as well as a novel regulator of normal plant growth and development, while significantly increasing plants' defense costs.

Dislocation Majorana bound states in iron-based superconductors.

We show that lattice dislocations of topological iron-based superconductors such as FeTe1-xSex will intrinsically trap non-Abelian Majorana quasiparticles, in the absence of any external magnetic field. Our theory is motivated by the recent experimental observations of normal-state weak topology and surface magnetism that coexist with superconductivity in FeTe1-xSex, the combination of which naturally achieves an emergent second-order topological superconductivity in a two-dimensional subsystem spanned by screw or edge dislocations. This exemplifies a new embedded higher-order topological phase in class D, where Majorana zero modes appear around the "corners" of a low-dimensional embedded subsystem, instead of those of the full crystal. A nested domain wall theory is developed to understand the origin of these defect Majorana zero modes. When the surface magnetism is absent, we further find that s± pairing symmetry itself is capable of inducing a different type of class-DIII embedded higher-order topology with defect-bound Majorana Kramers pairs. We also provide detailed discussions on the real-world material candidates for our proposals, including FeTe1-xSex, LiFeAs, ß-PdBi2, and heterostructures of bismuth, etc. Our work establishes lattice defects as a new venue to achieve high-temperature topological quantum information processing.

The experiences of children and adolescents with cancer returning to school: A qualitative meta-synthesis.

BACKGROUND: Returning to school can be challenging for children and adolescents with cancer who have been absent for a long time. As there is little known about the return to school experience of children and adolescents with cancer, this meta-synthesis aimed to describe the experiences of children and adolescent cancer patients as they return to school. METHODS: Seven English databases and three Chinese databases were searched from inception to March 14, 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to appraise study quality. Data were synthesized using the Thomas and Harden thematic and content analysis method. RESULTS: Twelve qualitative studies met the inclusion criteria and were analyzed into meta-synthesis. Data synthesis led to constructing four analytical themes and twelve sub-themes. The four major themes constructed were:benefits to school re-entry, barriers to school re-entry, motivators to school re-entry and the adaptation process after returning to school. CONCLUSION: Children and adolescents with cancer were willing to return to education and can adapt to school life over time. But they were faced with challenges, including physical, psychological, and social barriers. Appropriate measures need to be taken to reduce those barriers. IMPLICATIONS TO PRACTICE: Findings can be used to inform future research and interventions to support a successful return to education for children and adolescents with cancer. Healthcare providers should address the needs of children and adolescents at different stages and actively work with schools, hospitals and families to help childhood cancer survivors successfully return to school.

Effects of long-term blue light irradiation on carotenoid biosynthesis and antioxidant activities in Chinese cabbage (Brassica rapa L. ssp. pekinensis).

The aim of this study was to investigate the impact of long-term exposure to blue light-emitting diodes (LEDs) on the accumulation of indolic glucosinolates and carotenoids, as well as the plant growth and antioxidant activities in both orange and common Chinese cabbage (Brassica rapa L. ssp. pekinensis). Blue light treatment also induced higher ferric-reducing antioxidant power and 2,2-diphenyl-1-picrylhydrazyl by 20.66 % and 30.82 % and antioxidant enzyme activities catalase, peroxidase, superoxide dismutase, and the accumulation of non-enzymatic antioxidant substances (total phenols and total flavonoids) in the orange Chinese cabbage. Furthermore, long-term exposure to blue light had negative effects on the net photosynthetic rate and chlorophyll fluorescence levels. Meanwhile, blue light promoted accumulation of Indol-3-ylmethyl glucosinolate (I3M), ß-carotene, lutein and zeaxanthin due to the high expression of regulatory and biosynthetic genes of the above metabolic pathways. In particular, lycopene and ß-carotene content in orange Chinese cabbage increased by 60.14 % and 65.33 % compared to the ones in common line. The accumulation of carotenoid and increasing antioxidant levels in the orange cabbage line was influenced by long-term blue light irradiation, leading to better tolerance to low temperature and drought stresses. The up-regulation of transcription factors such as BrHY5-2, BrPIF4 and BrMYB12 may also contribute to the increased tolerance in orange Chinese cabbage to extreme environmental stresses. The BrHY5-2 gene could activate carotenoid biosynthetic genes and induce the accumulation of carotenoids. These findings suggested that long-term blue light irradiation could be a promising technique for increasing the nutrition value and enhancing tolerance to low temperature and drought stresses in Chinese cabbage.

Emergent ferromagnetism with superconductivity in Fe(Te,Se) van der Waals Josephson junctions.

Ferromagnetism and superconductivity are two key ingredients for topological superconductors, which can serve as building blocks of fault-tolerant quantum computers. Adversely, ferromagnetism and superconductivity are typically also two hostile orderings competing to align spins in different configurations, and thus making the material design and experimental implementation extremely challenging. A single material platform with concurrent ferromagnetism and superconductivity is actively pursued. In this paper, we fabricate van der Waals Josephson junctions made with iron-based superconductor Fe(Te,Se), and report the global device-level transport signatures of interfacial ferromagnetism emerging with superconducting states for the first time. Magnetic hysteresis in the junction resistance is observed only below the superconducting critical temperature, suggesting an inherent correlation between ferromagnetic and superconducting order parameters. The 0-π phase mixing in the Fraunhofer patterns pinpoints the ferromagnetism on the junction interface. More importantly, a stochastic field-free superconducting diode effect was observed in Josephson junction devices, with a significant diode efficiency up to 10%, which unambiguously confirms the spontaneous time-reversal symmetry breaking. Our work demonstrates a new way to search for topological superconductivity in iron-based superconductors for future high Tc fault-tolerant qubit implementations from a device perspective.

Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism.

Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred antihypertensive treatment. Therefore, antihypertensive drugs have become some of the most commonly prescribed drugs in healthcare settings. However, antihypertensive drugs have different effects on bone metabolism. The results of animal and clinical studies on the effects of antihypertensive drugs on osteoporosis or fracture risk are controversial and have aroused widespread concern among clinicians. Recent studies found that angiotensin receptor blockers, selective ß-adrenergic receptor blockers, and thiazide diuretics might improve bone trabecular number and bone mineral density by stimulating osteoblast differentiation, reducing osteoclast generation, and other mechanism. Furthermore, nonselective ß-adrenergic receptor blockers and dihydropyridine calcium channel blockers were found to have no significant relationship with bone mineral density or bone strength, and α-adrenergic receptor blockers and loop diuretics might increase fracture risk by decreasing bone mineral density. This article aimed to review previous animal experiments, clinical studies, and meta-analyses focusing on the effects of different antihypertensive drugs on bone metabolism, and to provide a new approach for the prevention and treatment of osteoporosis.

Development and feasibility of a theory-guided and evidence-based physical activity intervention in pregnant women with high risk for gestational diabetes mellitus: a pilot clinical trial.

BACKGROUND: Physical activity has been utilized as an effective strategy to prevent gestational diabetes mellitus (GDM). However, most pregnant women with high risk for GDM did not achieve the recommended physical activity level. Furthermore, relevant physical activity protocols have varied without theory-guided and evidence-based tailored to pregnant women with high risk for GDM. This study aimed to develop and pilot test a theory-guided and evidence-based physical activity intervention protocol for pregnant women with high risk for GDM. METHODS: The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention (the MRC framework). The preliminary protocol for physical activity intervention was developed based on self-efficacy theory, research evidence identified from systematic reviews and clinic trials, stakeholder engagement, context, and economic considerations. The preliminary intervention protocol was validated through a content validity study by an expert panel of 10 experts. A single-blinded randomized controlled trial (RCT) was designed to test the feasibility and acceptability of the intervention. RESULTS: The validity of the preliminary intervention protocol was excellent as consensus was achieved. The final 13 sessions of self-efficacy enhancing physical activity intervention protocol were developed, including knowledge education, exercise clinic visits and video, and group discussions with face-to-face and online blended sessions. In the feasibility study, 34 pregnant women with high risk for GDM were randomized for the intervention (n = 17) or the control group (n = 17). The recruitment and retention rates were 82.9% and 58.9%, respectively. Women in the intervention group had a lower incidence of GDM (26.7% vs. 36.5%) than the control group (P >0.05). All participants were satisfied with the intervention and agreed that the intervention was helpful. CONCLUSIONS: The developed self-efficacy-enhancing physical activity intervention is a feasible and acceptable intervention for enhancing physical activity among pregnant women with high risk for GDM and is ready to be tested in a more extensive RCT study. TRIAL REGISTRATION: The study was registered on 4 February 2022 (ChiCTR2200056355) by the Chinese Clini Trial Registry (CHiCTR).

Advanced progress of the relationship between PCSK9 monoclonal antibodies and hyperglycemic adverse events.

Purpose of Review: Long-term use of statins had been confirmed to cause an increase in hyperglycemic adverse events (HAEs), whose mechanism has been well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK9-mAbs), a kind of new lipid-lowering drug, can effectively reduce plasma low-density lipoprotein cholesterol levels in patients with CHD and have been widely used. However, animal experiments, Mendelian randomization studies, clinical researches and Meta-analyses which focused on the relationship between PCSK9-mAbs and HAEs had reached different conclusions, which has attracted great attention from clinicians. Recent Findings: The newest FOURIER-OLE randomized controlled trial followed PCSK9-mAbs users for over 8 years, whose results suggested that long-term use of PCSK9-mAbs did not increase the incidence of HAEs. Newest Meta-analyses also indicated that there was no relationship between PCSK9-mAbs and NOD. Meanwhile, genetic polymorphisms and variants related to PCSK9 might have effects on HAEs. Conclusion: According to the results of current studies, there is no significant relationship between PCSK9-mAbs and HAEs. However, longer-term follow-up studies are still needed to confirm it. Although PCSK9 genetic polymorphisms and variants may affect the possible occurrence of HAEs, there is no need to perform relevant genetic testing before applying PCSK9-mAbs.

The Accumulation of Health-Promoting Nutrients from Representative Organs across Multiple Developmental Stages in Orange Chinese Cabbage.

Orange Chinese cabbage (Brassica rapa L. ssp. pekinensis) is an excellent source of health-promoting nutrients that could reduce the risk of chronic diseases. This study mainly investigated the accumulation patterns of eight lines of orange Chinese cabbage for indolic glucosinolates (GLSs) and pigment content from representative plant organs across multiple developmental stages. The indolic GLSs were highly accumulated at the rosette stage (S2), especially in inner and middle leaves, and the order of indolic GLSs accumulation in non-edible organs was flower > seed > stem > silique. The expression levels of biosynthetic genes in light signaling, MEP, carotenoids, and GLS pathways were consistent with the metabolic accumulation patterns. The results of a principal component analysis show a clear separation of high indolic GLS lines (15S1094 and 18BC6) from low indolic GLS lines (20S530). A negative correlation between the accumulation of indolic GLS and carotenoids was identified in our study. Our work contributes to providing valuable knowledge required to breed, grow, and select orange Chinese cabbage varieties and their eatable organs with higher nutritional value.

Young patients show poor efficacy for immune checkpoint inhibitor combined therapy in metastatic gastrointestinal cancers.

Background: The impact of age on the efficacy and safety of immunotherapy remains controversial. The previous studies simply classified patients into younger and older groups, which might not reflect the real impact of young age on immunotherapy efficacy. The current study aimed to explore the efficacy and safety of immune checkpoint inhibitor (ICI) combined therapy in young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) patients with metastatic gastrointestinal cancers (GICs), and further determine the role of immunotherapy in young patients. Methods: Patients with metastatic GIC including esophageal cancer (EC), gastric cancer (GC), hepatocellular cancer (HCC), and biliary tract cancer (BTC) who received ICI combination therapy were enrolled, divided into young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups. The clinical characteristics, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared among three groups. Results: A total of 254 patients were finally included, with 18, 139, and 97 cases in the young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups, respectively. Compared to middle-aged and old patients, young patients had lower DCR (all p < 0.05) and also had inferior PFS (p < 0.001) and OS (p = 0.017). The multivariate analyses showed that young age was an independent prognostic factor for PFS [hazard ratio (HR) 3.474, 95% confidence interval (CI) 1.962-6.150, p < 0.001] and OS (HR 2.740, 95% CI 1.348-5.570, p = 0.005). Subsequent safety analyses referring to irAEs demonstrated no significant differences for distribution frequency among each age group (all p > 0.05), whereas patients with irAEs displayed better DCR (p = 0.035) and PFS (p = 0.037). Conclusion: Younger GIC patients (aged 18-44 years) showed poor efficacy for ICI combined therapy, and irAEs could be used as a clinical biomarker to predict ICI efficacy in metastatic GIC patients.

Topological superconducting vortex from trivial electronic bands.

Superconducting vortices are promising traps to confine non-Abelian Majorana quasi-particles. It has been widely believed that bulk-state topology, of either normal-state or superconducting ground-state wavefunctions, is crucial for enabling Majorana zero modes in solid-state systems. This common belief has shaped two major search directions for Majorana modes, in either intrinsic topological superconductors or trivially superconducting topological materials. Here we show that Majorana-carrying superconducting vortex is not exclusive to bulk-state topology, but can arise from topologically trivial quantum materials as well. We predict that the trivial bands in superconducting HgTe-class materials are responsible for inducing anomalous vortex topological physics that goes beyond any existing theoretical paradigms. A feasible scheme of strain-controlled Majorana engineering and experimental signatures for vortex Majorana modes are also discussed. Our work provides new guidelines for vortex-based Majorana search in general superconductors.

The effects of short term blue light treatment on promoting nutrition value in Chinese cabbage.

Chinese cabbage is a nutrients-rich vegetable with diverse leaf colors. Here, we used widely-targeted metabolomics technology to study the metabolic responses of three Chinese cabbage varieties with representative leaf colors after blue light treatment. The inner leaf color of orange varieties 20S530 and 15S1094 changed from yellow to golden yellow, while no visible color change occurred in the common variety 14S23 after the treatment. A total of 844 metabolites were measured from the leaf samples of these three varieties in a time course study after short term blue light treatment, with kaempferol-4'-O-glucoside, isoquercitrin, hyperin, arbutin, sulforaphane as enriched nutritional metabolites. Orange Chinese cabbage varieties showed additional nutrition enhancement after the treatment. This study is the first to explore the global metabolic responses of Chinese cabbage after blue light treatment, and our findings provided valuable insights on how to effectively use lighting conditions to enhance specific groups of nutrients in vegetables.

Safety and effectiveness of apatinib in elderly patients with metastatic gastric cancer: a sub-analysis from the large-scale, prospective observational study of apatinib for gastric cancer treatment in a real-world clinical setting (AHEAD-G202).

Background: Apatinib was shown to improve the survival of Chinese patients with refractory metastatic gastric cancer (mGC). As an orally administered drug, it has been widely used in elderly patients because the dosing schedule can be adjusted flexibly. However, data on the efficacy and safety of apatinib in elderly patients is scarce. The aim of this study was to evaluate the toxicity and effectiveness of apatinib for elderly patients with mGC in a real-world setting. Methods: Data from the sub-population of patients who were ≥65 years enrolled in the AHEAD-G202 trial were analyzed. Patients with mGC were prospectively registered and initially received ≤850 mg oral apatinib daily combined or not combined with chemotherapy, at the investigator's discretion. The primary endpoint was safety. The secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 117 patients were included. There were 51 (43.59%) patients in the low-dose (250 mg) group, 60 (51.28%) patients in the mid-dose (425 to 500 mg) group, and 6 (5.13%) patients in the high-dose (850 mg) group according to the initial daily doses. Hypertension (6.84%) was the only grade 3-4 adverse event (AE) with a prevalence of more than 5% and across the low-dose (11.76%), mid-dose (3.33%) and high-dose group (0%). The median OS and PFS were 7.13 months (95% CI: 5.04 to 9.22 months) and 4.27 months (95% CI: 3.24 to 5.29 months), respectively. The OS and PFS were similar among the 65-74 and ≥75 years groups (χ2=1.406, P=0.306; χ2=0.378, P=0.066, respectively). The OS and PFS were also comparable among the 3 dose groups. Conclusions: Elderly patients with mGC can tolerate and benefit from apatinib therapy. A lower initial daily dosing strategy may be a suitable choice for elderly patients in clinical practice.

Comparison of Efficacy and Safety of Taxanes Plus Platinum and Fluorouracil Plus Platinum in the First-Line Treatment of Esophageal Cancer: A Systematic Review and Meta-Analysis.

Fluoropyrimidine plus platinum (FP) and taxanes plus platinum (TP) are standard treatments for esophageal cancer (EC). This systematic review and meta-analysis aim to explore the difference in the therapeutic effect and toxicity of FP and TP regimens in EC patients. PubMed, Embase, and Cochrane were fully searched and analyzed to find relevant articles on EC patients treated with FP and TP regimens up to 22 March 2022. Thirty-one studies, with a total of 3432 participants, were included in this review. The primary outcomes showed that the prognosis and therapeutic efficacy of TP groups were better than those of FP groups for the EC patients treated with definitive chemoradiotherapy treatment (3-year OS: RR: 1.25, 95% CI: 1.08−1.44, p = 0.003; 3-year PFS: RR: 1.43, 95% CI: 1.17−1.75, p = 0.0006; ORR: RR: 1.17, 95% CI: 1.06−1.29, p = 0.001). However, TP therapy was significantly correlated with a higher incidence of leukopenia and thrombocytopenia (p < 0.05). In the preoperative neoadjuvant chemoradiotherapy group, these two groups had a similar survival time (p > 0.05). The FP regimen corresponded to a higher incidence of thrombocytopenia, while the TP regimen was associated with an increased incidence of febrile leukopenia (p < 0.05). Therefore, TP regimens could generate both superior clinical response and survival benefits when compared with FP regimens in EC patients undergoing definitive chemoradiotherapy.

Clinical course and management of insidious adrenal crisis manifested initially as hyperpyrexia secondary to pembrolizumab: Case reports and literature review.

Immune checkpoint inhibitors (ICIs) are novel drugs with a dramatic survival benefit in patients with advanced malignancies. With the widespread use, several immune-related adverse events (irAEs) have emerged, which may be life-threatening. Herein we report two patients with adrenal crisis who received anti-programmed cell death protein 1 (PD-1) (pembrolizumab) therapy. Several reports of secondary adrenal insufficiency caused by pembrolizumab exist, including during treatment or late onset. Severe adrenal insufficiency according to the Common Terminology Criteria for Adverse Events (CTCAE) has rarely been described in the literature, since it initially manifests as high-grade fever. The two male patients developed adrenal crisis that was first characterized by hyperpyrexia accompanied by abdominal symptoms. These initial manifestations confused the clinicians who misdiagnosed them as infection. Timely identification, hydrocortisone pulse therapy, and fluid resuscitation improved the patients' condition. Compliance with the standardized treatment approach and course can prevent or relieve the crisis as soon as possible. Assessment of relevant laboratory test results and patient education, including when to use stress-dose hydrocortisone and guidance on route of administration, can reduce the incidence of adrenal crisis. We report these two cases and have evaluated the literature on previously reported cases to improve our understanding of this condition and offer a more scientific approach to diagnosis and treatment options.

Growth hormone associated with treatment efficacy of immune checkpoint inhibitors in gastric cancer patients.

Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been widely employed to improve the outcome of gastric cancer patients. In the present study, the impact of posttreatment growth hormone (GH) levels on the treatment efficacy of ICIs for advanced gastric cancer (AGC) patients was assessed. Methods: Seventy-five AGC patients treated with anti-PD-1 antibodies at The Fourth Hospital of Hebei Medical University were involved. We divided AGC patients into two groups as high-GH group and low-GH group based on the GH level. Immunotherapy efficacy was assessed in terms of objective response rate, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) based on the National Comprehensive Cancer Network Guidelines. The enumeration data were compared by χ 2 test or Fisher's exact test. Survival curves were drawn by the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. Results: The higher GH levels were associated with a lower DCR of ICIs with a DCR of 30.0% in the high-GH group and 53.3% in the low-GH group (P = 0.046). The subsequent univariate analysis showed that a high GH level was associated with both shorter PFS (P = 0.016) and shorter OS at the borderline statistical level (P = 0.052) in AGC patients treated with ICIs. Cox model analysis also proved that the GH level was an independent risk factor for the outcome of AGC patients (PFS: P = 0.013, HR, 2.424, 95% CI, 1.202-4.890; OS: P = 0.014, HR, 3.301, 95% CI, 1.279-8.519). Conclusions: The post-treatment GH level might be a predictor for ICIs treatment in AGC patients.

A self-efficacy-enhancing physical activity intervention in women with high-risk factors for gestational diabetes mellitus: study protocol for a randomized clinical trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Evidence has demonstrated that moderate-intensity physical activity may reduce the risk of gestational diabetes. However, women at risk of GDM spend most of their time performing sedentary behaviors. Although researchers identified self-efficacy as a mediator to overcome physical activity barriers, exercise intervention during pregnancy based on self-efficacy theory has not been discussed so far. Furthermore, there is conflicting evidence regarding the effects of a physical exercise intervention on the incidence of GDM and other maternal or neonatal outcomes in women at higher risk for GDM. METHODS/DESIGN: A single-center, parallel, randomized controlled trial will be conducted in a maternal-child health care center. A total of 244 pregnant women at high risk for GDM will be randomized into a study group receiving a self-efficacy-enhancing physical activity intervention or a control group receiving the usual care. The intervention will consist of four group sessions and everyday reminders by WeChat (Tencent, Shenzhen, China). The program will begin at approximately 13-14+6 gestational weeks and end at 36+6 gestational weeks. The primary outcomes will include the incidence of GDM, blood sugar values, and physical activity. The secondary outcomes will include physical activity self-efficacy, gestational weight gain, maternal outcomes, and neonatal outcomes. DISCUSSION: The findings of this research will contribute toward understanding the effects of a self-efficacy theory-oriented physical activity program on the incidence of GDM, blood sugar values, physical activity level, gestational weight gain, physical activity self-efficacy, maternal outcomes, and neonatal outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry (CHiCTR) ChiCTR2200056355 . Registered on February 4, 2022.